miR-29b Modulates Intestinal Epithelium Homeostasis by Repressing Menin Translation

Menin regulates distinct cellular functions by regulating gene transcription through its interaction with partner transcription factors, but the exact mechanisms that control Menin levels remain largely unknown. Here we report that Men1 mRNA, encoding Menin, is a novel target of microRNA-29b (miR-29b) and that miR-29b/Men1 mRNA association regulates Menin expression posttranscriptionally in rat intestinal epithelial cells (IECs). Overexpression of a miR-29b precursor lowered modestly the levels of Men1 mRNA, but reduced robustly the de novo synthesis of Menin; conversely, antagonization of miR-29b enhanced Menin protein synthesis and steady-state levels. The repressive effect of miR-29b on Menin expression was mediated through a single binding site in the coding region of Men1 mRNA, since point mutation of this site prevented miR-29b-induced repression of Menin translation. Increasing cellular polyamines due to overexpression of ornithine decarboxylase (ODC) enhanced Menin translation by reducing miR-29b, whereas polyamine depletion by inhibiting ODC increased miR-29b, thus suppressing Menin expression. Moreover, an increase in Menin abundance in miR-29b-silenced population of IECs led to increased sensitivity to apoptosis, which was prevented by silencing Menin. These findings indicate that miR-29b represses translation of Men1 mRNA, in turn affecting intestinal epithelial homeostasis by altering IEC apoptosis.

Source: BJ Cell - October 15, 2014 Category: Biochemistry Authors: M Ouyang, W Su, L Xiao, J N Rao, L Jiang, Y Li, D J. Turner, M Gorospe, J Wang Tags: BJ Cell Source Type: research